AU2005221602B2

AU2005221602B2 - Cerebral temperature control

Info

Publication number: AU2005221602B2
Application number: AU2005221602A
Authority: AU
Inventors: Mats Allers; Fredrik Boris-Moller; Anders Lunderqvist; Tadeusz Wieloch
Original assignee: Quickcool AB
Current assignee: Quickcool AB
Priority date: 2004-03-16
Filing date: 2005-03-16
Publication date: 2010-05-20
Anticipated expiration: 2025-03-16
Also published as: EP1729702A1; CN1946359A; AU2005221602A1; JP4871256B2; US20050209662A1; EP1729702B1; CN1946359B; CA2559625A1; US7189253B2; JP2007529267A; WO2005087156A1

Description

WO 2005/087156 1 PCT/SE2005/000382 TITLE: CEREBRAL TEMPERATURE CONTROL 5 Technical field of the invention The present invention refers to the control of the temperature of the brain of a human being, and especially to cooling of the brain. 10 Background of the invention In pathological conditions, the body temperature or the temperature of body parts of a human being influences the healing process and the risk of permanent damage. Can cer cells, for example, are heat sensitive and a local 15 heating of the blood flow around a cancer tumor may for some types of cancer constitute a treatment resulting in restrained tumor growth or in some cases even in a shrink ing of the tumor. In other cases cooling of a body part may be important to reduce adverse secondary symptoms of the 20 pathological condition, this is primarily intended for the treatment of brain ischemia. In the case of a stroke, the blood flow to the brain is reduced (ischemia) due to a hemorrhage or the clogging of a blood vessel. This condition will cause permanent 25 functional deficits unless treatment to restore blood flow and protect nerve cells is initiated at an early stage, which will reduce the loss of bodily functions, such as pa ralysis. It is well known that cooling the brain effec tively blocks the development of cellular damage after an 30 episode of ischemia.

WO 2005/087156 2 PCT/SE2005/000382 Whole body cooling of the patient suffering transient circulatory arrest to the brain results in a reduction of the symptoms of neurological deficit. However, there are certain problems associated with whole body cooling. One is 5 that the cooling is not fast enough to-effectively use its protective potential. Another problem is that whole body cooling must be carried out under close control of physio logical parameters or under anesthesia. Yet another problem is that there is a risk of cardiovascular complications. 10 In the case of a circulatory arrest, the brain can suffer permanent damage if the arrest exceeds a time period of about 5-15 minutes. However, if the temperature of the brain is lowered before, during or after the arrest, the brain damage is diminished. 15 In the case of brain trauma the brain suffers from open or close head concussion. Hypothermia has been shown to diminish traumatic brain injury in such cases. There are several methods in the prior art to carry out a more isolated cooling of a single organ or body part. 20 An example of cooling of the brain in a human being is dis closed in the patent document WO 98/23217, relating to a method of cerebral retro-perfusion and retro-infusion, in volving the cooling of arterial blood that then is returned to the entire brain. However, this method entails a large 25 and complicated surgical procedure, which delays the onset of an actual treatment. US 5,906,588 discloses a method and a device for heart-lung bypass and cooling of a specific body part. This disclosure primarily relates to complicated heart surgery 30 and organ transplantation.

WO 2005/087156 3 PCT/SE2005/000382 The US patent application 10/072,857 discloses a first phase comprising the step of introducing an infusion cathe ter for infusion of a temperature controlled infusion solu tion or perfusate into a vein initiating quick general body 5 hypothermia. An optional second phase may be used, wherein a second infusion catheter is'introduced into an artery of the human being, the second infusion catheter being config ured to provide selective temperature control of the brain and infusion of other important substrates and pharmacol 10 ogical compounds into the brain. A third phase is also dis closed, wherein an extra-corporeal circuit is established between a vein and an artery. Blood is withdrawn from the vein, and the temperature of the blood is modified outside the body and the blood is returned to the body through the 15 artery. In many animals, the brain can be protected from over heating by heat exchange over the rete mirabile at the base of the brain. Here a fine network of the carotid artery is in close connection to a similar network of veins draining 20 the brain. Respiratory evaporation from the surfaces of the nostrils and the epipharynx cools veins in this region flowing towards the rete mirabile whereby heat exchange can occur between arteries and veins. In animals without a rete mirabile, a variation of more or less complicated scrolls 25 of conchae in the nasal cavity enhances evaporation and the heat exchange. Flushing the nasal cavities with fluids have been shown to reduce the brain temperature (Natale J E et al Stroke 1989; 20:770-777, Hagioka S et al. Crit. Care. Med. 30 2003; 31:2502-2508). To prevent the flushing fluid to enter the trachea, however, tracheostomy or intubations are nec- WO 2005/087156 4 PCT/SE2005/000382 essary and still it would be difficult to prevent fluid to enter the esophagus. Disclosure of the invention 5 The present invention is based on the discovery that the cerebral arteries can temper the human brain by rem nants of the venous carotid rete, i.e. the cavernous and other sinuses, surrounding the carotid and other cerebral arteries, such as vertebral arteries, before entering the 10 brain. Cold air or fluids in the nasal cavities including the epipharynx are in close thermal contact with the veins draining to the dense venous plexus surrounding the inter nal carotid and vertebral arteries and to the cavernous si nus. Moreover, the sub mucosal position of the carotid ar 15 teries in the epipharynx might play an additional role in this heat exchange. The hypothesis is supported by Mariak Z et al. (J. Appl Physiol 1999; 87:1609-13) who demonstrated a slight fall of the brain temperature when intubated patients (no 20 cold venous blood from nasal cavities) were extubated and were allowed to breathe normally and this in spite of the poor heat conduction of air. According to the present invention, a selective hypo thermia treatment of the brain in patients with brain 25 ischemia, such as stroke and cardiac arrest, is disclosed, and a technique that can also include patients with hyper thermia. This technique can also be used for increasing the temperature of the brain. An object of the present invention is to provide a 30 system and a method for quick and efficient control of the WO 2005/087156 5 PCT/SE2005/000382 temperature of the brain without substantially changing the temperature of the rest of the body. Another object of the invention is to provide a system and a method that is simple and initially does not require 5 specialized personnel acquainted with for example radiology .or other diagnostic imaging techniques. In a first aspect of the invention, there is provided a system for indirect temperature regulation of substan tially the brain of a human being via a nasal cavity 10 thereof, comprising a membrane adapted to be arranged in contact with a surface of said nasal cavity, said membrane defining a closed volume; an inlet means for introducing fluid into said volume and an outlet means for removing fluid from said volume; and means for circulating said 15 fluid into said volume via said inlet means and out of said volume via said outlet means. The system may further com prise a cooling member for introducing temperature regu lated fluids into said nasal cavities, whereby said fluid can be either in direct contact with said nasal cavities or 20 separated from said nasal cavities by said membrane. In an embodiment, the system comprises a double lumen catheter means introduced through a nostril of a human be ing and placed with its tip adjacent the back of said nasal cavities, said double lumen catheter means comprising a 25 first lumen and a second lumen, said first and second lu mens being in fluid communication by means of a- set of openings, said second lumen being configured as an expand able balloon; a reservoir comprising a fluid; and means for circulating said fluid from said reservoir into said double 30 lumen catheter means and back to said reservoir or to a re ceptacle, whereby said balloon, when in use, is expandable WO 2005/087156 6 PCT/SE2005/000382 to cover the inner surface of the nasal cavity. A tempera ture regulator may be connected to the reservoir, said regulator being configured to regulate the temperature of said fluid, via a cooling device. The means for circulating 5 said temperature regulated fluid may comprise a set of tub ings configured to connect said catheter means to said res ervoir or said receptacle. In another embodiment, the double lumen catheter means may comprise: an inlet in fluid communication with said reser 10 voir and with said first lumen, said inlet being configured to receive said fluid from said reservoir; said first lumen having a set of distal end openings in a front end portion of said catheter means, said end openings being arranged in fluid communication with said second lumen; and an outlet 15 in fluid communication with said second lumen and with said reservoir or said receptacle. The inlet and outlet may be arranged at a proximal portion of the catheter means. The circulation of said fluid may be accomplished by means of hydrostatic pressure of said fluid in said reservoir. Al 20 ternatively, the means for circulating said fluid further may comprise a pumping means arranged between said reser voir and said catheter means. The means for circulating the fluid may be configured to provide a flow rate of approxi mately 25 - 1000 ml/min. The system may further comprise a 25 pressure regulating nozzle arranged at said tubings adja cent said reservoir or said receptacle, said pressure regu lating nozzle being configured to provide a resistance in said tubings, said pressure regulating nozzles being possi bly variable. 30 In a further embodiment, the system may further comprise a temperature monitoring device configured to, indirectly or WO 2005/087156 7 PCT/SE2005/000382 directly, register the temperature of the brain and to automatically control said temperature regulator to regu late the temperature of said fluid in said reservoir, via a heat exchanging device, in order to maintain the tempera 5 ture of the brain at a desired level. The temperature moni toring device may be an IR thermistor, a MR device, a Near InfraRed device or an impedance spectroscopy device. The temperature monitoring device may be arranged on the skin, such as the forehead, of the human being or in an auditory 10 canal of the human being. The temperature of the brain may be approximately 10 - 41'C, such as 20-35"C. The catheter means may be manufactured of a material such as plastic, synthetic latex, silicone or Gore-Tex. The material may be coated with a hydrophilic surface or an anaesthetic agent. 15 In another aspect of the invention, there is provided a kit of disposables for use in the system mentioned above, com prising a plurality of tubings and double lumen catheter means. In a further aspect, there is provided a method for indi 20 rect temperature regulating of substantially the brain of a human being via a nasal cavity thereof, comprising the steps of: introducing a double lumen catheter means through a nostril into said nasal cavity of said human being, said double lumen catheter means comprising a first lumen and a 25 second lumen, said first and second lumens being in fluid communication by means of a set of openings, said second lumen being configured as an expandable balloon; placing said catheter means with its tip adjacent the back portion of said nasal cavity; temperature regulating a fluid in a 30 reservoir; circulating said fluid from said reservoir into said double lumen catheter means back to said reservoir or WO 2005/087156 8 PCT/SE2005/000382 to a receptacle, whereby said balloon is expanded to cover the inner surface said nasal cavity. The step of circulat ing said fluid may comprise the step of pumping said fluid from said reservoir into said catheter means and back to 5 said reservoir via said first and second lumens by means of a pumping means. The step of circulating said fluid may be accomplished by means of the hydrostatic pressure of said fluid in said reservoir. The fluid may circulate at a flow rate in the interval of approximately 25 - 1000 ml/min. 10 In an embodiment, the method may further comprise the step of placing a temperature sensor on the human being; di rectly or indirectly registering a brain temperature by means of said temperature sensor; and temperature regulat ing said fluid, via a heat exchanging device, in dependence 15 of said registered brain temperature in order to maintain the brain temperature at a desired level. The step of tem perature regulating said fluid may comprise the step of cooling said fluid in order to obtain a brain temperature of approximately 10 - 41"C, preferably 20-35'C. 20 In a still further aspect, there is provided a system for indirect temperature regulation of substantially the brain of a human being via a nasal cavity thereof, comprising: a first balloon catheter means introduced through a first nostril into said nasal cavity, said first balloon catheter 25 comprising a first balloon and a second balloon, said first balloon being placed at the back of said nasal cavity and being configured to occlude the nasal entrance to the mouth, said second balloon being placed at the opening of said first nostril and being configured to occlude said 30 first nostril; a second balloon catheter means introduced through a second nostril of said nasal cavity, said second WO 2005/087156 9 PCT/SE2005/000382 balloon catheter comprising a third balloon placed at the opening of said second nostril and being configured to oc clude said second nostril; a reservoir comprising a fluid; and means for circulating said fluid from said reservoir 5 into said first nostril, through several holes in said first balloon catheter means into said nasal cavity, whereby said fluid flushes said nasal cavity and leaves through said second nostril by means of said second balloon catheter means, or the other way around. 10 In a yet further aspect, there is provided a method for in direct temperature regulating of substantially the brain of a human being via a nasal cavity thereof, comprising the steps of: introducing a first balloon catheter means through a first nostril of a human being, where said first 15 balloon catheter comprises a first balloon and a second balloon; placing said first balloon at the back of said na sal cavity and said second balloon at the opening of said first nostril; expanding said first balloon to occlude the nasal entrance to the mouth and expanding said second bal 20 loon to occlude said first nostril; introducing a second balloon catheter means through a second nostril of a human being, where said second balloon catheter comprises a third balloon; placing said third balloon at the opening of said second nostril; expanding said third balloon to occlude 25 said second nostril; temperature regulating a fluid in a reservoir; and circulating said fluid from said reservoir through said first nostril and into said nasal cavity and back through said second nostril, or the other way around. In still yet a further aspect, there is provided a system 30 for indirect temperature regulation of substantially the brain of a human being via nasal and mouth cavities WO 2005/087156 10 PCT/SE2005/000382 thereof, comprising: a first balloon catheter means intro duced through a first nostril of said nasal cavity, said first balloon catheter comprising a first balloon placed at the opening of said first nostril and being configured to 5 occlude said first nostril; a second balloon catheter means introduced through a second nostril of said nasal cavity, said second balloon catheter comprising a second balloon placed at the opening of said second nostril and being con figured to occlude said second nostril; a third balloon 10 catheter means introduced through said mouth cavity, said third balloon catheter comprising a third balloon placed in mid oesophagus of the human being and being configured to occlude said mid oesophagus; a catheter mean placed in said mouth cavity and sealed to the lips of the mouth of the hu 15 man being; a reservoir comprising a fluid; and means for circulating said fluid from said reservoir into said first and second nostril, through said first and second balloon catheter means into said nasal cavity, whereby said fluid flushes said nasal cavity and leaves through said mouth by 20 means of said catheter means. In another further aspect, there is provided a method for indirect temperature regulating of substantially the brain of a human being via nasal and mouth cavities thereof, com prising the steps of: introducing a first balloon catheter 25 means through a first nostril of said nasal cavity, said first balloon catheter comprising a first balloon; placing said first balloon at the opening of said first nostril; expanding said first balloon to occlude said first nostril; introducing a second balloon catheter means through a sec 30 ond nostril of said nasal cavity, said second balloon catheter comprising a second balloon; placing said second WO 2005/087156 PCT/SE2005/000382 balloon at the opening of said second nostril; expanding said second balloon to occlude said second nostril; intro ducing a third balloon catheter means through said mouth cavity, said third balloon catheter comprising a third bal 5 loon; placing said third balloon in mid oesophagus of said human being; expanding said third balloon to occlude said mid oesophagus; introducing a catheter means into said mouth cavity; sealing said catheter means to the lips of said mouth cavity; temperature regulating a fluid in a res 10 ervoir; and circulating said fluid from said reservoir into said first and second nostrils, through said first and sec ond balloon catheter means into said nasal cavity, flushing said fluid through said nasal cavity and through said mouth cavity by means of said catheter means. 15 In a yet further aspect, there is provided a system for in direct temperature regulation of substantially the brain of a human being via a nasal cavity thereof, comprising: a balloon catheter means introduced through a nostril into said nasal cavity, said balloon catheter comprising a first 20 balloon, a second balloon and an opening means, said first balloon being placed at the back of said nasal cavity adja cent a distal end of a nasal septum in said nasal cavity and being configured to occlude said nasal cavity, said second balloon being placed at the opening of said first 25 nostril and being configured to occlude said first nostril, said opening being placed adjacent said second balloon; a reservoir comprising a fluid; and means for circulating said fluid from said reservoir into said nostril, through said opening means into said nasal cavity, whereby said 30 fluid flushes said nasal cavity and leaves said nostril by WO 2005/087156 12 PCT/SE2005/000382 means of several holes in said balloon catheter means, or the other way around. In a still yet further aspect, there is provided a method for indirect temperature regulating of substantially the 5 brain of a human being via a nasal cavity thereof, compris ing the steps of: introducing a first balloon catheter means through a nostril into said nasal cavity, where said first balloon catheter comprises a first balloon, a second balloon and an opening means; placing said first balloon at 10 the back of said nasal cavity adjacent a distal end of a nasal septum of said nasal cavity, said second balloon at the opening of said nostril and said opening means adjacent said second balloon; expanding said first balloon to oc clude said nasal cavity and expanding said second balloon 15 to occlude said first nostril; temperature regulating a fluid in a reservoir; and circulating said fluid from said reservoir into said first nostril, through said opening means into said nasal cavity, flushing said fluid through said nasal cavity and through said nostril by means of sev 20 eral holes in said first balloon catheter means, or the other way around. By means of the present invention, the naso-pharyngeal membranes can be temperature regulated, e.g. cooled or heated, whereby the cold or heat is transmitted to the ad 25 jacent arterial and venous structures, which in turn is transmitting the cold or heat to the brain. In this way, the temperature of the brain parenchyma can be reduced or increased without needing any direct contact or interven tion with the vascular system. 30 WO 2005/087156 13 PCT/SE2005/000382 Brief description of the drawings Further objects, features and advantages will become evident from the following description of several embodi ments of the invention with reference to the enclosed draw 5 ings, in which: Fig 1 is a schematic view of a first embodiment of a system according to the present invention; Fig 2 is a schematic view of a second embodiment of a system according to the present invention; 10 Fig 3 is a cross-sectional view of the double catheter means arranged at the inner surface of the nose, the nasal cavity, and epipharynx of a patient; Fig 4 is a diagram showing an example of the regis tered temperature variation in the brain as a function of 15 the time, when the inventive system and method is applied to a laboratory animal in the form of a pig; Fig 5 is a schematic view of two temperature sensors, each of which is arranged in an auditory channel; Fig 6A is a cross-sectional view of another embodiment 20 of a system according to the present invention; Fig 6B is a cross-sectional view similar to Fig 6A of the other nasal cavity; Fig 6C is a cross-sectional view similar to Fig 6A of yet another embodiment of the invention; 25 Fig 7 is a top view of the head including the embodi ment shown in Fig 6A-6B; Fig 8 is a diagram of different combinations of cool ing techniques; Fig 9A is a cross-sectional view of still another em 30 bodiment of the invention; and WO 2005/087156 14 PCT/SE2005/000382 Fig 9B is a cross-sectional view of one more embodi ment of the invention. Detailed description of the invention 5 The present invention will now be described with ref erence to the accompanying drawings. Fig 1 discloses a first embodiment of an inventive system 10 for cerebral temperature control of a human be ing, in which embodiment the system comprises one double 10 lumen catheter means 30. Fig 2 shows schematically a second embodiment of the inventive system, which system comprises two double lumen catheters means 30a, 30b to be introduced in respective nostril of a human being. By means of two catheter means, 15 temperature regulation may be accomplished more effectively and quicker. In the figures, the same reference numerals are used to indicate corresponding components. Further, in Fig 2, the corresponding components and details of the respective 20 catheter means are distinguished by means of the addition of the letter a respective b to the reference numeral. Ar rows are used to show the flow direction of the fluid in the system. However, as understood by the skilled person, the fluid flow can have the opposite direction to that in 25 dicated in the drawings. The system 10 comprises a double lumen balloon cathe ter means 30, 30a, 30b configured to be introduced through a nostril of a human being and to be placed with its tip at the level of the back of the nasal cavities, as shown in 30 Fig 3. Pushing a sleeve or sheath 39 backward or forward may vary the length of double lumen balloon catheter.

WO 2005/087156 15 PCT/SE2005/000382 The double lumen catheter means 30, 30a, 30b com prises a first lumen 32, 32a, 32b and a second lumen 38, 38a, 38b. The first and second lumens are arranged in fluid communication with each other by means of a set of end 5 openings 34, 34a, and 34b. The second lumen 38, 28a, 38b is configured as an expandable balloon. The system 10 could also comprise a temperature regulator 24, shown in Fig 2, connected to a reservoir 20 comprising a fluid 22. The temperature regulator 24 is con 10 figured to regulate the temperature of the fluid 22 com prised in the reservoir. The fluid 22 is for example a sa line solution. The temperature regulator controls a heat exchanging device, normally a cooling device, for tempera ture regulating the fluid. 15 Means are arranged in the form of tubes 12, 12a, 12b, 14, 16, 16a, 16b for circulating said temperature regulated fluid 22 from the reservoir 20 to the catheter means 30, 30a, and 30b. The means 12, 12a, 12b, 14, 16, 16a, 16b are configured to circulate the fluid 22 into the first lumen 20 32, 32a, 32b of the catheter means 30, 30a, 30b, from the first lumen 32, 32a, 32b into the second lumen 38, 38a, 38b, and from the second lumen 38, 38a, 38b back to said reservoir 20, or vice versa. The circulation means 12, 12a, 12b, 14, 16, 16a, 16b 25 for circulating said temperature regulated fluid 22 com prises a set of tubings 12, 12a, 12b, 14, 16, 16a, 16b con figured to connect the catheter means 30, 30a, 30b to the reservoir 20. In use, when the fluid enters the second catheter 38, 30 38a, 38b, the second catheter 38, 38a, 38b is expanded more or less as a balloon to completely or almost completely WO 2005/087156 16 PCT/SE2005/000382 cover the inner surface of the nose and epipharynx, as shown in Fig 3, whereby the naso-pharyngeal membranes may be temperature regulated. The temperature is transferred to adjacent arterial and venous structures, which are trans 5 ferring the temperature to the brain. Further, by means of the inventive arrangement the temperature regulated fluid 22 circulates in a closed fluid system 12, 12a, 12b; 14; 16, 16a, 16b; 30a, 30b; 20. The inventive double lumen catheter means 30, 30a, 30b 10 comprises an inlet 31, 31a, 31b arranged to provide fluid communication with the reservoir 20 and with the first lu men 32, 32a, and 32b. The inlet 31, 31a, 31b is further configured to receive an amount of the temperature regu lated fluid 22 from the reservoir 20. The first lumen 32, 15 32a, 32b has a set of distal end openings 34, 34a, 34b in a front-end portion 36, 36a, 36b of the catheter means 30, 30a, and 30b. The end openings 34, 34a, 34b being arranged to provide fluid communication with said second lumen 38, 38a, and 38b. The catheter means 30, 30a, 30b further com 20 prises an outlet 33, 33a, 33b configured to provide fluid communication with the second lumen 38, 38a, 38b and with the reservoir 20. The inlet 31, 31a, 31b and the outlet 33, 33a, 33b are arranged at an end portion 40, 40a, 40b of the catheter 25 means 30, 30a, 30b. According to an embodiment, the second lumen 38, 38a, 38b has a variable length L of approximately 5 - 25 cm. The sleeve 39 around the shaft of the catheter can reduce the length L of the second lumen when the sleeve is moved back 30 ward or forward. In expanded state, the diameter A of the second lumen at a front part 36, 36a, 36b of the second lu- WO 2005/087156 17 PCT/SE2005/000382 men is approximately 2 - 4 cm and the diameter B of the second lumen at a base part 37, 37a, 37b of the second lu men is approximately 1 - 3 cm, but these measures can vary if the balloon pressure is increased. 5 The catheter means 30, 30a, 30b could be manufactured of a flexible material such as plastic, synthetic latex, silicone or Gore-Tex. The material may be coated with a substance resulting in a hydrophilic surface. An anesthetic agent may also cover the surface. 10 According to an embodiment of the invention, the circulation of the fluid 22 is accomplished by means of the hydrostatic pressure of the fluid 22 in the reservoir 20. As shown in Fig 1, the reservoir 20 is arranged at a level, which is higher than the nasal cavity of the human being 15 under treatment, and a waste bag 29 is arranged below the same level. Thence, the cold fluid flows by gravity from the reservoir and to the catheter device and further to the waste bag. However, according to another embodiment of the inven 20 tion, the means 12, 14, 16 for circulating the temperature .regulated fluid 22 further comprises a pumping means 18 ar ranged between the reservoir 20 and the catheter means 30, 30a, 30b by means of tubings 12, 12a, 12b, 14. Thus, it should be understood that the pumping means 18 illustrated 25 in Fig 2 is optional. The circulation means for circulating the fluid is preferably configured to provided a fluid flow rate of 25 1000 ml/min. The inventive system can also comprise a pressure 30 regulating nozzle 26, 26a, 26b, shown in Figs 1 and 2, ar ranged at the tubings 16, 16a, and 16b. The pressure regu- WO 2005/087156 18 PCT/SE2005/000382 lating nozzle 26, 26a, 26b is arranged close to the reser voir 20 or the waste bag 29 and being configured to provide a resistance in the tubings, whereby the fluid flowing in the system is able to expand the second lumen 38, 38a, 38b. 5 The nozzle may be a clamp that is adjustable. Moreover, pressure sensors 49 may be arranged for measuring the pressure in the second lumen, as shown in Fig 1. Such a pressure sensor may be a similar construction as the second lumen arranged in a side branch. By means of the 10 pressure sensor, it can be assured that the pressure will not be too high, which may be experienced to be uncomfort able. The pressure sensor may as well be conventional pres sure meters. The technique according to the present invention in 15 volves the following, as shown in Fig 3. Two double lumen thin walled balloon catheters are inserted into the nos trils of the patient. When inflated and circulated with fluid, e.g. saline, at a temperature of ±0 to 41 0 C, preferably 20-35"C, at a rate of 25 to 1000 ml per min, the 20 lower range for neonate, the balloons will cover the inner surfaces of the nose and the epipharynx, collectively named the nasal cavities. Circulation can be performed in either direction. Cooling of the nasal cavities can then be accom plished without any fluids entering the trachea or the 25 esophagus. Different sizes of catheters and balloons will fit neonates to adults and a sheath or sleeve around the shaft of the catheter can reduce the length of the balloon when the sheath is moved forward. In an alternative embodiment shown in Fig 6A and 6B, a 30 double balloon catheter 60, shown in Fig 6A, which has a balloon 62 at its distal end and is introduced into a nos- WO 2005/087156 1 9 PCT/SE2005/000382 tril and advanced into the epipharynx. This balloon is pro vided with two small catheters (not shown), one for infu sion of cold fluids and the other for extraction of these fluids into the balloon. When this balloon is inflated and 5 retracted it lifts the soft palate, which then obliterates the passage between the nostrils and the epipharynx. At the same time this balloon acts in cooling the tissues at this level of epipharynx where especially the carotid artery lies very superficial. Another, more proximal balloon 64 on 10 this catheter obliterates the entrance to the same nostril when inflated. A single balloon catheter 68 is introduced into the other nostril, shown in Fig 6B, the balloon when inflated obliterates the nostril and the catheter ends im mediately distal to the balloon. 15 Multiple side holes on the double balloon catheter 60 between the balloons permit infusion of cold saline (0 25'C) for example at a rate of 25 - 1000 ml/ min into the nostrils. The fluid is evacuated through the other nostril catheter 68. The lumen of this catheter 68 has no connec 20 tion to the more distal balloon 70. The system can also comprise a temperature sensor 50, which is connectable to the temperature regulator 24 and configured to register or estimate the temperature of the brain and to automatically control the temperature regula 25 tor 24 to regulate the temperature of the fluid in the res ervoir 20 in order to maintain the temperature of the brain at a desired level. The temperature sensor is for example an IR thermistor, which could be arranged in an auditory canal of the human being or on the skin, such as the fore 30 head, of the human being. The temperature could also be monitored by a MR device, a Near Infrared device or an im- WO 2005/087156 2 0 PCT/SE2005/000382 pedance spectroscopy device. The desired brain temperature level may be approximately 10 - 350C. The temperature level depends on the degree of hypothermia, which is clinically relevant. If the brain temperature is increased it should 5 be closely monitored. The present invention also relates to a kit of dispos ables for use in the inventive system. The kit comprises a plurality of tubings, and the double lumen catheter means 30, 30a, 30b. 10 The invention relates also to a method for cerebral temperature control. The method comprises the steps of: introducing the double lumen catheter means 30, 30a, 30b through the nostril of the human being; placing the catheter means 30, 30a, 30b with its tip 15 at the level of the back of the nasal cavities; temperature regulating the fluid 22 in the reservoir 20; circulating the fluid from the reservoir into a first lumen 32, 32a, 32b of the catheter means, from the first 20 lumen into a second lumen 38, 38a, 38b of said catheter means, and from said second lumen back to said reservoir, whereby the second lumen is expanded like a balloon to com pletely cover the inner surface of the nasal cavities and epipharynx and whereby said temperature regulated fluid 25 circulates in a closed fluid system. The step of circulating said temperature regulated fluid could also comprise a step of pumping said fluid from said reservoir, to said catheter means and back to said reservoir via said first and second lumens by means of a 30 pumping means.

WO 2005/087156 21 PCT/SE2005/000382 The temperature-regulated fluid circulates at a flow rate in the interval of approximately 25 - 1000 ml/min, de pending of the size of the human being. The flow could be at the lower range for neonates. 5 The method can further comprise the steps of using a temperature sensor for registering the brain temperature and regulating the fluid in dependence of said registered brain temperature in order to maintain the brain tempera ture at a desired level. 10 The step of temperature regulating said fluid com prises the step of cooling said fluid in order to obtain a brain temperature of approximately 10 - 35'C. Fig 4 schematically shows how the registered tempera ture in the left and right brain hemisphere is reduced af 15 ter the onset of the inventive method, while the registered temperature in the rectum remains almost unchanged. In the performed experiment, a double lumen catheter means was in troduced in respective nostril of an experimental animal. The temperature regulator controls the fluid temperature to 20 desired level through a cooling element. Circulation of cold fluid started approximately at 10:18 and stopped ap proximately at 10:41 (after 23 minutes). As seen from Fig 4 the registered temperature in the left and right brain hemisphere is reduced within a short period of time after 25 the start and increases again after the stop. Further, the temperature of the rectum is almost unchanged. Thus, a se lectively cooling of the brain is accomplished. As an example, another embodiment of the invention will now be described with reference to Figs 6A and 6B. A 30 double balloon catheter 60, shown in Fig 6A, is introduced through one nostril. The inner or distal balloon 62, when WO 2005/087156 22 PCT/SE2005/000382 expanded, fixates the soft palatinum and occludes the en trance to the mouth. The distal balloon is supplied with fluid by two small diameter catheters, one for infusion of cold saline, and the other for extraction of the same 5 fluid. A pressure regulating nozzle keeps the balloon ex panded. The cold saline cools the area around the expanded distal balloon. The second or proximal balloon 64 is configured to oc clude the nostril. 10 A second balloon catheter 68 (see Fig 6B) is placed into the other nostril, the second balloon catheter 68 hav ing a proximal balloon 70 configured to occlude the nos tril. A'temperature regulated fluid, e.g. cold saline, is 15 injected into the first catheter 60 and leaves through side holes 66 arranged lengthways the first catheter 60. The cold saline flushes the cavum nasae and epipharynx and passes beyond the wall between the two nasal cavities and leaves through the contra lateral nostril, whereby the 20 naso-pharyngeal membranes are temperature regulated. Other alternative designs may include that the distal balloon 62 is arranged in the nasal cavity closer to the nostril, somewhere in front of the end of the nasal septum, delimiting only a portion of the nasal cavity, as shown in 25 Fig 6C. The cooling fluid may enter the delimited portion of the nasal cavity via the catheter 60 and holes 66 therein and leave via a separate outlet catheter 69 adja cent the proximal balloon 64 (not shown in the drawings). The introduction of these balloon catheters into the 30 nostrils of the patient will make rapid selective brain cooling possible. At the arrival into the hospital admis- WO 2005/087156 23 PCT/SE2005/000382 sion, suitable alternatives (see Fig 8) for the continua tion of the hypothermia treatment are decided according to the condition of the patient. Paramedic's start at the site an intravenous infusion 5 of ice cooled lactated Ringers solution, possibly combined with naso-pharyngeal cooling or the treatment starts with naso-pharyngeal cooling alone. Depending on the condition of the patient at the arri val to the hospital the following alternatives for future 10 treatment can be seen in the admission flow chart according to Fig 8. Patients with naso-pharyngeal cooling or retro perfu sion treatment at the admission unit are later referred to the ward for future treatment according to Fig 8. 15 Another embodiment is used for patients with tracheo stomy or tracheal intubation, shown in Fig 9A and 9B, re spectively, where an esophageal balloon catheter 80 is in troduced through the mouth and the balloon 81 is inflated in mid esophagus. Further balloon catheters 68', 68'', same 20 as described in connection with Fig 6B, are placed into each nostril and the balloons 70', 70'' are inflated to oc clude the nostrils. A large diameter catheter 82, not shown, is placed in the mouth and sealed to the lips for example with the aid of tapes. Cold, 5-25"C, Ringer lactate 25 fluid or saline solution is infused through the catheters 68' into the nasal cavities at the rate of 100-1000 ml/min and evacuated through the catheter 82 in the mouth to a container. Flushing the muscosal cavities of the nose, epipharynx, pharynx and mouth with cold solution will act 30 in the same way as described above.

WO 2005/087156 24 PCT/SE2005/000382 It should be understood that the pumping means, tub ings, fluid reservoir, temperature regulated means or other elements described above can be used in the last-mentioned embodiments. 5 According to the invention, the tissue in the nose and epipharynx are cooled, either with direct contact with a cooling fluid (Fig 6A) or via a membrane in contact with the tissue. In the present specification and claims, the expression "nasal cavity" is used to mean all inside sur 10 face of the nose (via both nostrils) and including the epipharynx. In some embodiments, only a portion of the na sal cavity surfaces is used for cooling purpose, and this is intended to be within the scope of the invention. The cooling effect of the fluid can be monitored by 15 measuring the inlet and outlet temperature of the fluid as well as the flow rate, as indicated in Fig 6C with tempera ture measuring unit AT connected to a thermocouple arranged in the inlet and outlet openings. By calorimetric calcula tions, the cooling effect can be calculated. If it is pre 20 sumed that the heat generation of the brain or tissue in side the head is relatively constant, the temperature de crease can be calculated or predicted. Furthermore, temperature measurements at different places of the body and with different methods as indicated above, can provide 25 further data for a closer prediction of the brain tempera ture. The intention of the invention is to cool substan tially only the brain, including adjacent tissue, but main tain the temperature of the rest of the body at normal tem 30 perature. It may be that the body temperature may also be lowered and this tendency may be counteracted by covering 25 part of the body by a blanket or by providing slightly heated warm air. The present invention has been described with reference to embodiments and an example. However, it should be understood that modifications of components or functional steps could be performed without deviating from the scope of the invention. With reference to the use of the word(s) "comprise" or "comprises" or "comprising" in the foregoing description and/or in the following claims, unless the context requires otherwise, those words are used on the basis and clear understanding that they are to be interpreted inclusively, rather than exclusively, and that each of those words is to be so interpreted in construing the foregoing description and/or the following claims.

Claims

1. A system for cerebral temperature control of a living being, comprising: a first double lumen balloon catheter configured to be introduced through a nostril of a living being; said double lumen balloon catheter comprising: a first lumen and a second lumen, said first and second lumens being in fluid communication by means of respective openings, said second lumen being configured as an expandable first balloon; a second double lumen balloon catheter configured to be introduced through another nostril of said living being; said second double lumen balloon catheter comprising a third lumen and a fourth lumen, said third and fourth lumens being in fluid communication by means of respective openings, said fourth lumen being configured as an expandable second balloon; a temperature regulator connected to a reservoir comprising a fluid, said temperature regulator being configured to regulate the temperature of said fluid; a circulation mechanism operative to pass said temperature regulated fluid to each of said first and second catheters from said reservoir into said first lumen, from said first lumen into said second lumen, and out from said second lumen, and from said reservoir into said third lumen, from said third lumen into said fourth lumen, and out from said fourth lumen, whereby said first and second balloons, when in use, are expandable to cover the inner surfaces of the nose.

2. The system of claim 1, wherein said temperature regulated fluid is circulated in a closed fluid system.

3. The system of claim 1, further comprising a pressure regulating nozzle located in the tubing at the reservoir, said pressure regulating nozzle being configured to provide a resistance in the tubing.

4. The system of claim 1, further comprising a temperature sensor positionable in an auditory canal of a living being, to provide an estimate of the temperature of the brain and 27 to control the temperature regulator to regulate the temperature of the fluid in the reservoir.

5. The system of claim 4, wherein said desired brain temperature level is approximately

31-32 degrees Celsius. 6. The system of claim 1, wherein said first double lumen balloon catheter is configured to be introduced through the nostril of a living being to a position which is not further than adjacent the level of the back of the tongue. 7. The system of claim 1, wherein said second double lumen balloon catheter is configured to be introduced through the nostril of a living being to a position which is not further than adjacent the level of the back of the tongue. 8. The system of claim 1, wherein said circulation of said fluid is accomplished by the hydrostatic pressure of said fluid in said reservoir, or said circulation mechanism further comprises a pump connected by tubing between said reservoir and said catheters, or said circulation mechanism comprises tubing connecting said catheters to said reservoir. 9. The system of claim 1, wherein each of said double lumen balloon catheters comprises: an inlet in fluid communication with said reservoir and with said first lumen, said inlet being configured to receive said fluid from said reservoir; said first lumen having a set of distal end openings in a front end portion of said first catheter said end openings being arranged in fluid communication with said second lumen; and an outlet in fluid communication with said second lumen and with said reservoir. 10. The system of claim 9, wherein said inlet and outlet are arranged at an end portion of said first catheter. 11. A method for cerebral temperature control, comprising the steps of: introducing a double lumen balloon catheter through a nostril of a living being; 28 placing said catheter adjacent the level of the back of the tongue; regulating the temperature of a fluid in a reservoir; circulating said temperature regulated fluid from said reservoir into a first lumen of said catheter from said first lumen into a second lumen of said catheter and from said second lumen back to said reservoir, whereby the balloon is expanded to cover the inner surface of the nose. 12. The method of claim 11, wherein said step of circulating said temperature regulated fluid comprises the step of pumping said fluid from said reservoir to said catheter and back to said reservoir via said first and second lumens by a pump. 13. The system of claim I or method of claim 11, wherein said temperature regulated fluid circulates at a flow rate in the range of approximately 200-1000 ml/min. 14. The method of claim 11, further comprising the steps of: placing a temperature sensor in an auditory canal of the living being; estimating the brain temperature by means of said temperature sensor; and regulating the temperature of the fluid in dependence of said estimated brain temperature. 15. The method of claim 14, wherein the step of regulating the temperature of the fluid comprises the step of cooling said fluid in order to obtain a brain temperature of approximately 31-32 degrees Celsius. 16. The system of claim I or method of claim 11, wherein said double lumen balloon catheter has a length of approximately 20 to 25 cm. 17. The system of claim I or method of claim 11, wherein said double lumen balloon catheter has a diameter at a front part of approximately 2 to 4 cm. 18. The system of claim I or method of claim 11, wherein said double lumen balloon catheter has a diameter at a base part of approximately I to 3 cm. 29 19. The method of claim 11, further comprising: circulating the temperature regulated fluid through a system of tubing; and regulating fluid pressure in the tubing by a pressure regulating nozzle located in the tubing at the reservoir, for providing a resistance in the tubing. 20. A kit of disposables comprising: two replacement double lumen balloon catheters when used in the system according to any one of the claims I to 10; and tubing configured for connecting the catheters to said reservoir, said catheters and said tubing being disposable after use. 21. The system of claim 1, substantially as hereinbefore described. 22. The method of claim 11, substantially as hereinbefore described. 23. The kit of claim 20, substantially as hereinbefore described. BA.7316A